Variations in nucleolar organizer regions during 9-10 dimethyl1-2 benzanthracene induced tongue carcinogenesis in rats

BACKGROUND: Many studies have reported the increased expression of epidermal growth factor receptor (EGFR) in various human malignancies and its association with the biologic behavior of the tumors. METHODS: We performed an immunohistochemical analysis of the EGFR in 217 cases of human esophageal squamous cell carcinoma, 161 lymph node metastases and 23 foci of squamous dysplasias. The findings were correlated with clinicopathologic features, including the clinical outcome. Southern blot analysis was performed in 42 cases for the detection of DNA amplification of the EGFR gene and subsequently was correlated with EGFR immunoreactivity. RESULTS: Epidermal growth factor receptor overexpression was detected in 71% of primary tumors and 88% of lymph node metastases, as compared to nonpathologic adjacent esophageal epithelium. Statistically significant correlations were observed between EGFR overexpression and sex, age, histologic type, and the presence of invasion. Tumor staining was classified into two patterns, homogeneous and heterogeneous, based on the distribution of EGFR-positive cells. The immunostaining patterns of primary tumors had a statistically significant correlation with histologic type, the presence of adventitial invasion, histologic stage and lymph node metastasis. There was a tendency toward a worse prognosis for those patients with EGFR overexpression in the primary tumor. Greater than 90% of the foci of squamous dysplasia demonstrated homogeneous EGFR overexpression. DNA amplification of the EGFR was observed in 21% of primary tumors, and all demonstrated immunohistochemical overexpression. CONCLUSIONS: Immunohistochemical overexpression of the EGFR, which was more frequent than EGFR DNA amplification, appears to play an important role in biologic behavior of human esophageal squamous cell carcinomas.     

Risk factors for low birth weight and intrauterine growth retardation in Santiago, Chile

An epidemiologic case-control study to ascertain the determinants of low birthweight was carried out in Santiago, Chile, from January to December 1989. The cases were defined as livebirths < 2500 g. The controls were livebirths > or = 2500 g of birthweight. All cases and a random sample (1:1) of controls were selected among 8,254 singleton births occurring at the El Salvador Hospital in the Eastern area of Santiago. These deliveries represented 50% of institutional deliveries in the area. Home deliveries (2%) and private hospital deliveries were not included in the study. Information was obtained from hospital medical records by six trained medical students. Some information could not be obtained from the hospital medical records. Thus the second step in data collection was the tracking of all the selected subjects to their referring neighborhood health centers. For the analysis, the data were divided into 3 case (outcome) categories: 453 subjects were the total case group. From these, 153 were the IUGR case group and 300 were the LBW preterm case group. The general control group consisted of 605 normal birthweight infants. 565 were the IUGR control group and 40 were the preterm control group. A total of 25 risk factors showed a significant crude odds ratio for at least one of the groups. In the multivariate logistic regression analysis eight variables: No. of pregnancies, previous adverse outcomes, previous LBW, pregnancy maternal weight, No. of visits, month of first prenatal care visit, maternal smoking and intrahepatic cholestasis of pregnancy, were significantly associated with LBW after adjustment by confounding. Eight risk factors: IUGR in previous pregnancies, Previous adverse outcome, Maternal smoking, intrahepatic cholestasis, maternal pregnancy weight, maternal height, month first prenatal visit, No. of visit, were significant to IUGR. Only two variables: pregnancy weight, divorced mother, were significantly associated with low birth weight in the preterm group. The most relevant risk factors were included in stepwise logistic regression models carried out for the outcome LBW for the general group, term group and preterm group, in order to adjust by confounding. Adjusted odds ratios were then obtained. Prenatal care related factors and maternal adverse obstetric factors were at higher significance for LBW in the general and IUGR groups. Only nutritional factors were related to LBW in preterm group. Women who delivered a LBW or IUGR infant were more likely to have fewer pregnancies, a history of previous LBW, lower prepregnancy weight and lower gestational weight gain. ICP was associated with an elevated risk of LBW that was independent of gestational age.     

Multigrid solution of the nonlinear Poisson-Boltzmann equation and calculation of titration curves

Although knowledge of the pKa values and charge states of individual residues is critical to understanding the role of electrostatic effects in protein structure and function, calculating these quantities is challenging because of the sensitivity of these parameters to the position and distribution of charges. Values for many different proteins which agree well with experimental results have been obtained with modified Tanford-Kirkwood theory in which the protein is modeled as a sphere (reviewed in Ref. 1); however, convergence is more difficult to achieve with finite difference methods, in which the protein is mapped onto a grid and derivatives of the potential function are calculated as differences between the values of the function at grid points (reviewed in Ref. 6). Multigrid methods, in which the size of the grid is varied from fine to coarse in several cycles, decrease computational time, increase rates of convergence, and improve agreement with experiment. Both the accuracy and computational advantage of the multigrid approach increase with grid size, because the time required to achieve a solution increases slowly with grid size. We have implemented a multigrid procedure for solving the nonlinear Poisson-Boltzmann equation, and, using lysozyme as a test case, compared calculations for several crystal forms, different refinement procedures, and different charge assignment schemes. The root mean square difference between calculated and experimental pKa values for the crystal structure which yields best agreement with experiment (1LZT) is 1.1 pH units, with the differences in calculated and experimental pK values being less than 0.6 pH units for 16 out of 21 residues. The calculated titration curves of several residues are biphasic.     

Evaluation of a rapid immunochromatographic test for diagnosis of dengue virus infection

A rapid (<7-min) immunochromatographic test for immunoglobulin M (IgM) and IgG antibodies to dengue viruses was evaluated by using hospital admission and discharge sera from 124 patients. The reference laboratory diagnosis was based on the results of virus isolation, hemagglutination-inhibition assay (HAI), and enzyme immunoassay (EIA). By the standard assays, patients experienced primary dengue virus infection (n = 30), secondary dengue virus infection (n = 48), Japanese encephalitis (JE) virus infection (n = 20), or no flavivirus infection (n = 26). The rapid test demonstrated 100% sensitivity in the diagnosis of dengue virus infection and was able to distinguish between primary and secondary dengue virus infections through the separate determinations of IgM and IgG. For all patients with primary dengue virus infection a positive test for IgM to dengue virus and a negative test for IgG to dengue virus were obtained, whereas for 46 of 48 patients (96%) with secondary dengue virus infection, a positive test for IgG to dengue virus with or without a positive test for IgM to dengue virus was obtained. The remaining two patients with secondary dengue virus infection had positive IgM test results and negative IgG test results. Furthermore, the rapid test was positive for patients confirmed to be infected with different dengue virus serotypes (12 infected with dengue virus serotype 1, 4 infected with dengue virus serotype 2, 3 infected with dengue virus serotype 3, and 2 infected with dengue virus serotype 4). The specificity of the test for nonflavivirus infections was 88% (3 of 26 positive), while for JE virus infections the specificity of the test was only 50% (10 of 20). However, most patients with secondary dengue virus infection were positive for both IgM and IgG antibodies to dengue virus, while no patients with JE virus infection had this profile, so cross-reactivity was only a concern for a small proportion of patients with secondary dengue infections. The rapid test demonstrated a good correlation with the reference EIA and HAI and should be useful for the rapid diagnosis of dengue virus infections.     

Antiendotoxin activity of cationic peptide antimicrobial agents

The endotoxin from gram-negative bacteria consists of a molecule lipopolysaccharide (LPS) which can be shed by bacteria during antimicrobial therapy. A resulting syndrome, endotoxic shock, is a leading cause of death in the developed world. Thus, there is great interest in the development of antimicrobial agents which can reverse rather than promote sepsis, especially given the recent disappointing clinical performance of antiendotoxin therapies. We describe here two small cationic peptides, MBI-27 and MBI-28, which have both antiendotoxic and antibacterial activities in vitro and in vivo in animal models. We had previously demonstrated that these peptides bind to LPS with an affinity equivalent to that of polymyxin B. Consistent with this, the peptides blocked the ability of LPS and intact cells to induce the endotoxic shock mediator, tumor necrosis factor (TNF), upon incubation with the RAW 264.7 murine macrophage cell line. MBI-28 was equivalent to polymyxin B in its ability to block LPS induction of TNF by this cell line, even when added 60 min after the TNF stimulus. Furthermore, MBI-28 offered significant protection in a galactosamine-sensitized mouse model of lethal endotoxic shock. This protection correlated with the ability of MBI-28 to reduce LPS-induced circulating TNF by nearly 90% in this mouse model. Both MBI-27 and MBI-28 demonstrated antibacterial activity against gram-negative bacteria in vitro and in vivo against Pseudomonas aeruginosa infections in neutropenic mice.     

Complications in surgical treatment of varicose veins of the lower limbs and their prevention]

To prevent hemorrhage and hematomas in the bed of subcutaneously removed large saphenous vein after Babcock the authors somewhat modified tactically the order of manipulations during the operative procedure. This method was employed while operating 42 patients with primary and secondary venous varices. It was feasible to prevent hemorrhage and hematomas along the vascular bed in every case. The suggested tactical modification of the removal of venous varices wound improve the postoperative course and shorten the terms of patients' stay at the hospital postoperatively.